Department of Anatomy, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Koeki Zaidan Hojin Tokyo-to Igaku Sogo Kenkyujo, Regenerative Medicine Project 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, Japan.
Brain Res. 2019 Jun 1;1712:167-179. doi: 10.1016/j.brainres.2019.02.016. Epub 2019 Feb 15.
Gonadal hormones contribute to brain sexual differentiation. We analyzed expression of progesterone receptor (PR), estrogen receptor-α (ERα), ERβ, and kisspeptin, in the preoptic area (POA) and/or the arcuate nucleus (ARC), in gonad-lacking steroidogenic factor-1 knockout (KO) mice during perinatal development. At postnatal-day (P) 0-P7, POA PR levels were higher in wild-type (WT) males compared with WT females, while those in KO males were lower than in WT males and similar to those in WT and KO females. At P14-P21, PR levels in all groups increased similarly. POA ERα levels were similar in all groups at embryonic-day (E) 15.5-P14. Those in WT but not KO males reduced during postnatal development to be significantly lower compared with females at P21. POA ERβ levels were higher in WT males than in WT females, while those in KO males were lower than in WT males and similar to those in WT and KO females at P0-P21. POA kisspeptin expression was female-biased in WT mice, while levels in KO females were lower compared with WT females and similar to those in WT and KO males. ARC kisspeptin levels were equivalent among groups at E15.5-P0. At P7-P21, ARC levels in WT but not KO males became lower compared with WT females. Diethylstilbestrol exposure during P0-P6 and P7-P13 increased POA PR and ERβ, and decreased POA ERα and ARC kisspeptin levels at P7 and/or P14 in both sexes of KO mice. These data further understanding of gonadal hormone action on neuronal marker expression during brain sexual development.
性腺激素有助于大脑的性别分化。我们分析了孕激素受体(PR)、雌激素受体-α(ERα)、ERβ 和 kisspeptin 在产前发育过程中缺乏类固醇生成因子-1 敲除(KO)小鼠的视前区(POA)和/或弓状核(ARC)中的表达。在出生后第 0-7 天(P),WT 雄性的 POA PR 水平高于 WT 雌性,而 KO 雄性的 PR 水平低于 WT 雄性且与 WT 和 KO 雌性相似。在 P14-P21,所有组的 PR 水平均相似增加。在胚胎第 15.5-14 天(E),所有组的 POA ERα 水平相似。在出生后发育过程中,WT 雄性而非 KO 雄性的 ERα 水平降低,至 P21 时明显低于雌性。POA ERβ 水平在 WT 雄性中高于 WT 雌性,而在 KO 雄性中低于 WT 雄性且与 WT 和 KO 雌性相似。在 WT 小鼠中,POA kisspeptin 的表达呈雌性优势,而 KO 雌性的表达水平低于 WT 雌性且与 WT 和 KO 雄性相似。在 E15.5-P0 时,ARC kisspeptin 水平在各组间相当。在 P7-P21,WT 雄性而非 KO 雄性的 ARC 水平低于 WT 雌性。在 P0-P6 和 P7-P13 期间暴露于己烯雌酚增加了 KO 小鼠的 POA PR 和 ERβ,降低了 POA ERα 和 ARC kisspeptin 的水平,在 P7 和/或 P14 在雌雄 KO 小鼠中。这些数据进一步了解了性腺激素在大脑性别发育过程中对神经元标记物表达的作用。